Repeated Physical Training and Environmental Enrichment Induce Neurogenesis and Synaptogenesis Following Neuronal Injury in an Inducible Mouse Model

Neuronal loss as a consequence of brain injury, stroke and neurodegenerative disorders causes functional impairments ranging from cognitive impairments to physical disabilities. Extensive rehabilitation and trainning may lead to neuroprotection and promote functional recovery, although little is known about the molecular and cellular mechanisms driving this event. To investigate the underlying mechanisms and levels of functional recovery elicited by repeated physical training or environmental enrichment, we generated an inducible mouse model of selective CA1 hippocampal neuronal loss. Following the CA1 neuronal injury, mice underwent one of the above mentioned conditions for 3 months. Exposure to either of these stimuli promoted functional cognitive recovery, which was associated with increased neurogenesis in the subgranular zone of dentate gyrus and enhanced synaptogenesis in the CA1 subfield. Notably, a significant correlation was found between the functional recovery and increased synaptogenesis among survived CA1 neurons. Collectively, these results support the utilization of cognitive and physical stimulation as approaches to promote recovery after neuronal loss and demonstrate the potential of this novel mouse model for the development of therapeutic strategies for various neurological disorders associated with focal neuronal loss.

吸入麻醉药在老年痴呆症小鼠的作用强度

背景随着人口老龄化，老年痴呆症确诊或初期接受手术患者越来越多。全身麻醉可能加重其症状和病理进展，所以让这些患者接受尽量少的麻醉药十分重要。因此我们需要了解老年痴呆症病理是否改变麻醉药物作用的强度。方法根据12-14月龄3XTgAD老年痴呆症模型小鼠和野生型C57BL6小鼠翻正反射消失的最小肺泡药物浓度来测定异氟烷、氟烷、七氟烷的诱导浓度和恢复时间。3XTgAD小鼠带有3处独立的突变：APPswe、taup301和PS1人类转基因，其中每一个转基因均与人类家族性老年痴呆症有关。结果3XTgAD小鼠对吸入麻醉药表现出轻微的抵抗作用（8％-30％），但是3种药物的恢复时间并没有差别。结论老年痴呆症所引起的基因易损性与神经病理学改变会使个体对3种吸入性麻醉药物的催眠作用的敏感性产生微小但明显的降低，但恢复时间没有改变。